Aminomethylation ammonia

In 1973, the unexpected transformation of 4-chloroethynyl-l,3,5-trimethylpy-razole under the action of sodium amide in liquid ammonia into 5-aminomethyl-4-ethynyl-l,3-dimethylpyrazole in 85% yield was reported (73IZV2166). Within... 

Aminomethyl-1-methyl-5-chloro-3(o-fluorophenyl)indole HCI Chromic anhydride Ammonia Hydrogen chloride... 

Ammonolysis of PET involves the reaction of PET with ammonia at temperatures of 70-180°C, usually under pressure in EG. The ammonolysis of PET postconsumer bottles has been canied out at temperatures in the range of 120-180°C and a pressure of ca. 2 MPa for 1-7 h. The TPA diamide formed may be converted to terephthalonitrile. Terephthalonitrile may be hydrogenated to form p-xylylenediamine and l,4-bis(aminomethyl)cyclohexane.12 A low-pressure PET ammonolysis process in EG has been developed. The process is catalyzed by 0.5 wt% zinc acetate at a temperature of 70°C and a PET-NH3 ratio of 1 6 (w/w). The yield of TPA diamide was 87%. 

However, with liquid ammonia or anhydrous methylamine 1,2,4-oxadiazines (88) are formed. 5-(Chloromethyl)-l,2,4-oxadiazoles (e.g., (86) react with urotropin to form salts, which are hydrolyzed with hydrochloric acid to 5-(aminomethyl) compounds (the Delepine reaction). Alternatively, 5-(aminomethyl)-l,2,4-oxadiazoles have been prepared by condensation of amidoximes with a-amino-acids <72JHC435>. 

A number of routes are available for the synthesis of 2,2 -bipyridines where one of the pyridine rings is built up from simpler entities. For example, condensation of 2-(aminomethyl)pyridine (31) with acetaldehyde or acetylene over a silicon-alumina catalyst at 450°C gives 2,2 -bipyridine, ° whereas 2-cyanopyridine reacts with acetylene at 120°C in the presence of a cobalt catalyst to afford 2,2 -bipyridine in 95% yield.2-Acetylpyridine with acrolein and ammonia gives 2,2 -bipyridine in the presence of dehydrating and dehydrogenating catalysts, and related condensations afford substituted 2,2 -bipyridines. ° In a similar vein, condensation of benzaldehyde with 2 mol of 2-acetylpyridine in the presence of ammonia at 250°C affords 2,6-di(2-pyridyl)-4-phenylpyridine, ° and related syntheses of substituted 2,2 6, 2"-terpyridines have been described. Likewise, formaldehyde with two moles of ethyl picolinoylacetate and ammonia, followed by oxidation of the product and hydrolysis and decarboxylation, affords a good... 

Like 2,2 - and 2,3 -bipyridines, 2,4 -bipyridine is formed by a number of reactions where one of the pyridine rings is built up from simpler components. Thus 4-(aminomethyl)pyridine with acetylene or acetaldehyde at 450"C affords 2,4 -bipyridine and 4-cyanopyridine reacts with acetylene at 120 C under pressure in the presence of a cobalt catalyst to give 2,4 -bipyridine in over 90% yield. 4-Acetylpyridine with acrolein and ammonia in the presence of dehydrating and dehydrogenating catalysts also gives 2,4 -bipyridine. A number of minor routes to 2,4 -bipyridine are worthy of... 

When ammonia or primary amines are used, the product amines may participate in further aminomethylation, resulting in the formation of a mixture of amines. Other byproducts (aldehydes, alcohols, carboxamides) may also be formed. The reaction to produce tertiary amines from secondary amines, however, is fairly selective. Aminomethylation of ethylene with piperidine was reported to form /V-propyl-piperidine with 75% yield when the reaction was carried out in the presence of [Fe(CO)5] and water without an external source of CO (170°C, 14 h).207... 

Hydrogenation of 4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-nitrile in tetrahydrofuran in the presence of ammonia over Raney nickel under 60 psi for 5 h yielded 3-aminomethyl-4//-pyrimido[2,l-a]isoquinolin-4-one (86EUP166439). Reduction of ethyl 4-oxo-4//-pyrimido[2,l-a]isoquino-line-3-carboxylate with diisobutylaluminum hydride in methylene chloride... 

Amylamine Aminopentane Aminomethyl-butane,CSHU NH2. Several isomers are known, including Isoamylamine,(CH,)2 -CH-CHj-CHj-NHj. They can be prepd by the reaction of amyl chlorides with ammonia in the presence of alcohol as a mutual solvent. Datta Chatterjee(Ref 2) detd expln temps of amylaminepicrate and amylamineperchlo-rate and found them to be 270° and 262°, respectively... 

In an initial step, 2-chloroacetic acid ethyl ester is reacted with formamide to give 5-methylimidazole-4-carboxylic acid ethyl ester. Then sodium in ammonia is used to convert that to 4-hydroxymethyl-5-methylimidazole-hydrochloride. Cysteamine HCI (HSCH2CH2NH2-HCI) is then reacted to give 4-(2-aminomethyl)-thiomethyl-5-methyl-imidazole dihydrochloride. Then N-cyanamido-5,5-dimethyl-dithio-carbonate (from cyanamid, KOH, CS2 and ((CH3)2S04) is reacted to give a further intermediate which is finally reacted with methylamine to give cimetidine. 

Acetic anhydride (7 ml) was added to a solution of 6.16 g of crude 2-aminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-lH-1,4-benzodiazepine in 200 ml of methylene chloride. The solution was added to 200 ml of saturated aqueous sodium bicarbonate and the mixture was stirred for 20 minutes. The organic layer was separated, washed with sodium bicarbonate, dried over sodium sulfate and evaporated to leave resinous 2-acetylaminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-IH -1,4-benzodiazepine. This material was heated with 40 g of polyphosphoric acid at 150°C for 10 minutes. The cooled reaction mixture was dissolved in water, made alkaline with ammonia and ice and extracted with methylene chloride. The extracts were dried and evaporated and the residue was chromatographed over 120 g of silica gel using 20% methanol in methylene chloride. The clean fractions were combined and evaporated to yield resinous 8-chloro-3a,4-dihydro-6-(2-fluorophenyl)-l- methyl-4H-imidazo[l,5-a][l,4] -benzodiazepine. 

The byproducts of the hydrogenation of adiponitrile are small amounts of hexahydroazepine, 1,2-diaminocyclohexane and 2-(aminomethyl)cyclopentylamine, besides acyclic secondary products. In an example of a continuous process, a 1 12.5 molar ratio of adiponitrile and ammonia that was mixed with 10-fold amount of a hydrogenated reaction mixture from a prior run to give a 1 44 adiponitrile-ammonia mixture... 

First of all, the steric hindrance may seriou,sly affect yield and/or stability of the product, when bulky substituents arc bound to the amine rcagent. Second, complications may arise, as we have seen before, with polyfunctional amines, mainly ammonia and primary amines, due to the pos.sibilily that the unrcacted hydrogen atoms of the amine may undergo further reaction with formaldehyde, thus producing undesired by-products. Similarly, the use of secondary bifunctional amines, such as piperazine, always leads to a bis-Mannich base, due to reaction of both amino groups. Attempts to limit the reaction to only one amine function, as well as hydrolysis of the Mannich product obtained from aminomethylation of mono-N-acylpiperazines, invariably gives the di.substituted piperazine 23. ... 

Compounds possessing labile hydrogen atoms readily condense with formaldehyde and an amine (primary or secondary) or ammonia, thereby placing an aminomethyl or substituted aminomethyl group at the location... 

On treatment with ammonia or primary amines, 6-substituted 2-chloromethyl-4-phenylquin-azoline 3-oxides 1 undergo rearrangement to 2-amino derivatives of 7-substituted 5-phenyl-3//-1,4-benzodiazepine 4-oxide 2, Reaction with secondary amines proceeds without rearrangement with formation of the expected 2-(aminomethyl)-4-phenylquinazoline 3-oxides (cf. Section 6.3.1.1.10.3.). 2o. s2i... 

CONDENSATION OF o -BROMOPROPIONYL (OR o-BROMOPHENYLACETYL) DERIVATIVES OF AMINOMETHYL KETONES WITH AMMONIA TO ACYLAMINOPYRAZINES... 

The limitations of this approach can be seen in the reaction of a saturated solution of ammonia in 90% ethanol with ethyl bromide in a 16 1 molar ratio, under which conditions the yield of primary amine was 34.2% (at a 1 1 ratio the yield was 11.3%). Alkyl amines can be one type of substrate that does give reasonable yields of primary amine (provided a large excess of NH3 is used) are a-halo acids, which are converted to amino acids. A-Chloromethyl lactams also react with amines to give good yields to the A-aminomethyl lactam. Primary amines can be prepared from alkyl halides by 10-43, followed by reduction of the azide (19-32), or by the Gabriel synthesis (10-41). 

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